The relationship of DNA damage to differential cytotoxicity is being determined in human cells exposed to chloroethylnitrosoureas, platinum complexes, and AZQ. Alkaline elution filter techniques are being used to measure DNA single strand breaks, DNA protein crosslinks and DNA interstrand crosslinks produced by these agents. DNA interstrand crosslinking has been found to correlate with decreased survival of cells unable to repair chloroethyl DNA monoadducts which subsequently form interstrand crosslinks in DNA in a delayed reaction. The ability to block DNA interstrand crosslinking may be related to 0(6) MeG repair systems present in normal and some tumor cells. This 0(6) MeG repair system may be missing in some tumor cells rendering these cells more susceptible to chloroethylnitrosourea therapy. This repair system does not appear to remove cis-platinum monoadducts, thus cis-Pt may be a useful alternative for chemotherapy of tumor cells resistant to chloroethylnitrosoureas.